Journal of Antimicrobial Chemotherapy最新文献

{"title":"Clinical outcomes of beta-lactam monotherapy versus beta-lactam plus azithromycin in hospitalized patients with community-acquired pneumoniae-right-to-reply.","authors":"Ilona Zhygalova Zhygalova, Iago Blanco López, Silvia Dopazo Sotillo, Uxía Carreira Sampayo, Pablo Rubiñán Iglesias, Adrián Sousa, Jorge Julio Cabrera Alvargonzález, Antonio Pérez-Landeiro, María Teresa Pérez-Rodríguez","doi":"10.1093/jac/dkag303","DOIUrl":"10.1093/jac/dkag303","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determinants of levofloxacin prophylaxis failure in high-risk haematology patients: a prospective study integrating resistant colonization and pharmacokinetic/pharmacodynamic target attainment.","authors":"Cemre Boşnak, Gökhan Metan, Pınar Zarakolu, Elifcan Aladağ Karakulak, Aslı Pınar, Hakan Göker, Jason A Roberts, Maria Patricia Hernandez-Mitre, Murat Akova","doi":"10.1093/jac/dkag284","DOIUrl":"10.1093/jac/dkag284","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the clinical and microbiological factors associated with the failure of levofloxacin prophylaxis in high-risk haematology patients, with a particular focus on the attainment of the pharmacokinetic/pharmacodynamic (PK/PD) target.</p><p><strong>Methods: </strong>This prospective case-control study evaluated adult high-risk haematology patients receiving levofloxacin prophylaxis (750 mg/day) during neutropenia. Analyses were performed at the episode level. Individual levofloxacin exposure was described using a population PK model, with the PK/PD target defined as fAUC0-24/MIC ≥80. Surveillance cultures were used to characterize Gram-negative bacterial (GNB) colonization and resistance profiles.</p><p><strong>Results: </strong>A total of 120 neutropenic episodes were analysed. Profound neutropenia was independently associated with prophylaxis failure (OR: 4.17; 95% CI: 1.70-10.2; P = 0.002], whereas achievement of fAUC/MIC ≥80 was independently associated with a reduced risk of failure (OR: 0.12; 95% CI: 0.02-0.62; P = 0.012). Receiver operating characteristic curve analysis identified fAUC/MIC ≥48.46 as the Youden-optimal cutoff (sensitivity 86.0%, specificity 38.3%; Youden J = 0.243). Achievement of this cutoff was also independently associated with a reduced risk of prophylaxis failure (OR: 0.26; 95% CI: 0.083-0.803; P = 0.019). Target non-attainment was strongly associated with levofloxacin-resistant GNB colonization, indicating that PK/PD failure was predominantly MIC driven.</p><p><strong>Conclusions: </strong>Levofloxacin prophylaxis failure appears to reflect an interplay between host factors and inadequate PK/PD target attainment, which was largely influenced by levofloxacin-resistant GNB colonization. The standard 750 mg dose was insufficient in a significant proportion of patients, supporting the need for prophylaxis strategies that integrate PK/PD targets and local resistance patterns.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148723532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors associated with virological failure in people with HIV treated with bictegravir/emtricitabine/tenofovir alafenamide. Impact of pre-existing mutations and risk of resistance emergence. ANRS-CO3-AquiVIH-NA cohort.","authors":"Pantxika Bellecave, Alaric Peyrouny-Mazeau, Olivier Leleux, Mojgan Hessamfar, Gwenaël Le Moal, Didier Neau, Laure Alleman, Charles Cazanave, Estibaliz Lazaro, Pierre Duffau, Marie-Anne Vandenhende, Bernard Castan, Camille Tumiotto, Fabrice Bonnet","doi":"10.1093/jac/dkag278","DOIUrl":"https://doi.org/10.1093/jac/dkag278","url":null,"abstract":"<p><strong>Objectives: </strong>We investigated, in a real-world setting, virological factors associated with virological failure (VF) after bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) initiation in people with HIV (PWH) with and without pre-existing drug resistance mutation (PRM) and the emergence of new resistance mutations at virological failure.</p><p><strong>Methods: </strong>Treatment-experienced PWH from ANRS-CO3-AquiVIH-NA cohort starting B/F/TAF between 2018 and 2021 were stratified depending on their baseline viral load (VL): virologically suppressed (VS; VL <50 copies/mL) and virologically unsuppressed (VU; VL >50 copies/mL). PRM were identified using cumulative genotypic resistance tests (GRT) according to the ANRS algorithm. Factors associated with VF were analysed using a Cox proportional hazards model and survival curves.</p><p><strong>Results: </strong>Among the 636 PWH with available GRT results, 82.7% were VS at B/F/TAF initiation. PRMs to at least one component of B/F/TAF were present for 23.1% of participants (20.9% VS and 33.6% VU), with the M184I/V mutation identified in 89.1% of cases (88.2% in VS and 91.9% in VU). Virological success was higher for those with no PRMs (92.8% no PRM vs 86.4% with PRM). VU PWH had a higher risk of VF [HR 9.53 (5.54-16.40)]. Among the 66 PWH with baseline GRT experiencing VF, new resistance mutations were selected for six (two VU and four VS). After VF, B/F/TAF was maintained for 56/66 (84.8%) participants, of whom 40/56 (71.4%) had a VL <50 copies/mL at their last visit.</p><p><strong>Conclusions: </strong>Virological suppression was maintained in VS PWH regardless PRMs but to a less extent in VU PWH. Emergence of new resistance mutation occurred rarely in the case of VF.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liposomal amphotericin B retrospective multicentre study on mycosis prophylaxis (L-AmB_RUSCO): tolerability and safety of extended-dosing primary antifungal prophylaxis in children with newly diagnosed acute myeloid leukaemia.","authors":"Erica Ricci, Alessio Mesini, Marcello Mariani, Giuseppina Aloj, Bianca Macri, Natalia Ana Mendoza-Palomar, Blanca Espinosa-López, Kim Buntrock, Kathrin Gordon, Francesco De Leonardis, Roberta Koronica, Laura Ferreras-Antolin, Hadeel Mahjoob, Adilia Warris, Thomas Lehrnbecher, Andreas H Groll, Elio Castagnola","doi":"10.1093/jac/dkag289","DOIUrl":"10.1093/jac/dkag289","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the tolerability and safety of extended-dosing liposomal amphotericin B (LAmB) as primary antifungal prophylaxis against invasive fungal disease (IFD) in children receiving chemotherapy for newly diagnosed acute myeloid leukaemia (AML); breakthrough proven or probable IFD was assessed as an exploratory secondary endpoint.</p><p><strong>Methods: </strong>This retrospective, multinational, multicentre observational study included children treated for newly diagnosed AML between January 2019 and December 2023. LAmB was administered according to local protocols at 1 mg/kg three times weekly, 2.5 mg/kg twice weekly or 5 mg/kg once weekly. Clinical and laboratory adverse events (AEs) were assessed to evaluate tolerability and safety. Breakthrough proven or probable IFD, defined according to EORTC/MSG criteria, was recorded as an exploratory secondary outcome.</p><p><strong>Results: </strong>Eighty-six courses of extended-dosing LAmB were analysed. The median age at first LAmB administration was 91 months (IQR 26-156). The median treatment duration was 13 weeks (IQR 3-21) at a median dose of 2.7 mg/kg per infusion, with a median estimated cumulative dose of 77.6 mg/kg (IQR 21.3-110.1). Clinical AEs occurred in 21% of courses, predominantly skin rash and lumbosacral pain. Laboratory AEs were mainly hypokalaemia (48%) and hepatotoxicity (19%), both dose related. Treatment discontinuation due to toxicity occurred in 15% of courses. Breakthrough proven or probable IFD occurred in 3% of cases.</p><p><strong>Conclusions: </strong>Extended-dosing LAmB represents a reasonably well-tolerated mould-active option for primary antifungal prophylaxis in children with newly diagnosed AML, particularly when triazoles are contraindicated or daily intravenous echinocandin administration is impractical; the low observed rate of breakthrough IFD should be interpreted cautiously given the absence of a comparator group.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: comparative nephrotoxicity of polymyxin B versus colistin: evidence from ensemble learning and propensity score matching.","authors":"Genzhu Wang, Xiangping Niu, Qiang Sun","doi":"10.1093/jac/dkag287","DOIUrl":"10.1093/jac/dkag287","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal spread of linezolid-, tigecycline-, and vancomycin-resistant Enterococcus faecium isolates co-harbouring transferable optrA, vanA and tet(M) variant.","authors":"Kaiqi Zeng, Weiyi Shen, Jiachang Cai","doi":"10.1093/jac/dkag292","DOIUrl":"10.1093/jac/dkag292","url":null,"abstract":"<p><strong>Objectives: </strong>This study investigated the clonal dissemination and molecular basis of linezolid-, tigecycline- and vancomycin-resistant E. faecium (LTVRE) isolates in a surgical intensive care unit (SICU) of a Chinese hospital.</p><p><strong>Methods: </strong>Three LTVRE isolates collected from patients in the SICU were subjected to antimicrobial susceptibility testing and whole-genome sequencing analysis. S1 nuclease pulsed-field gel electrophoresis was performed to verify the topology of plasmids. Conjugation experiments were conducted to evaluate the transferability of resistance determinants.</p><p><strong>Results: </strong>WGS analysis demonstrated that the three LTVRE belonged to the same clone (Sequence Type 78). The optrA and vanA genes were co-located on a transferable large linear plasmid (327.5 kb in size) and contributed resistance to linezolid and vancomycin. A tet(M) variant carrying a phenylalanine-to-isoleucine substitution at Position 473 (F473I) was identified within a Tn916-like transposon. Although chromosomally encoded, this element retains the capacity for horizontal transfer to E. faecium BM4105RF and conferred tigecycline resistance.</p><p><strong>Conclusions: </strong>Our findings reveal a resistance dissemination strategy in which plasmid-borne and chromosomal mobile genetic elements independently or cooperatively drive the spread of resistance to last-line antibiotics and highlight the urgent need for enhanced surveillance of multidrug-resistant E. faecium, such as LTVRE.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Group A Streptococcus molecular point of care testing in a paediatric emergency department.","authors":"Ewurabena A Mills, Rebekah Bingham, Ruud G Nijman, Shiranee Sriskandan","doi":"10.1093/jac/dkag290","DOIUrl":"10.1093/jac/dkag290","url":null,"abstract":"<p><strong>Background: </strong>An upsurge in Streptococcus pyogenes infections 2022-2023 highlighted potential benefits of point-of-care tests (POCT) to support clinical pathways, prevent outbreaks and optimize antibiotic use.</p><p><strong>Objectives: </strong>We conducted a pilot research study in a west London paediatric emergency department (ED) to determine whether a molecular POCT had potential to alter management in children who were also having a conventional throat swab taken for culture.</p><p><strong>Methods: </strong>Children <16 years presenting to ED who had a throat swab requested by a clinician were invited to have a second swab taken for research purposes only. Clinical management was unaffected by the research swab result, which was processed using a molecular POCT that was not approved for use in the host NHS Trust.</p><p><strong>Results: </strong>Prevalence of streptococcal infection was low during the study (May 2023-June 2025); swab positivity in symptomatic children was 12.8% (6/47). Overall, 38/49 (77.6%) participants who had throat swabs received antibiotics. Of those children recommended to receive antibiotics, 29/38 (76.3%) had a negative POCT. Mean time to reporting of positive throat swab culture results was 3.67 days (range 3-5 days) leading to occasional delay in treatment, although POCT identified positive results within minutes.</p><p><strong>Conclusion: </strong>Antibiotic use was frequent and could be avoided by use of a 'rule out' POCT in many children in the ED, provided suspicion of S. pyogenes is the main driver for prescribing. POCT were easy to process and produced immediate results compared with culture. More research is needed to establish whether POCT confers overall net benefit.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence and characterization of a novel plasmid co-harbouring tmexC3D2-toprJ2 and tet(X6) in Thiopseudomonas alkaliphila.","authors":"Shiqi Cao, Yuxuan Jia, Xiaoyu Lu, Panpan Wang, Xia Xiao, Zhiqiang Wang, Ruichao Li","doi":"10.1093/jac/dkag295","DOIUrl":"10.1093/jac/dkag295","url":null,"abstract":"<p><strong>Objective: </strong>The tmexCD-toprJ and tet(X) are key determinants mediating tigecycline resistance in bacteria, and investigating their epidemiological characteristics in different bacteria is crucial for controlling the spread of tigecycline-resistant bacteria. This study aimed to conduct a detailed investigation on the characterization of a Thiopseudomonas alkaliphila isolate SA1F2-1K carrying a novel plasmid co-harbouring tmexCD-toprJ and tet(X).</p><p><strong>Methods: </strong>An isolate SA1F2-1K co-harbouring tmexCD-toprJ and tet(X) was identified by PCR and was further characterized using antimicrobial susceptibility testing, conjugation and electroporation experiments, S1-PFGE, whole-genome sequencing and bioinformatic analysis.</p><p><strong>Results: </strong>A T. alkaliphila strain SA1F2-1K was isolated, which co-carried the tigecycline resistance gene cluster tmexC3D2-toprJ2 and the tet(X6) gene. This strain exhibited high-level resistance to tigecycline, kanamycin, florfenicol and tetracycline, and the tigecycline resistance genes of SA1F2-1K were non-transferable. S1-PFGE and whole-genome sequencing revealed that tmexC3D2-toprJ2 and tet(X6) were located on a novel untypable MDR plasmid pSA1F2-1K_200k. Genetic environment analysis showed that the acquisition of tmexC3D2-toprJ2 and tet(X6) might be associated with the △umuC gene and △ISCR2 element, respectively. Phylogenetic analysis indicated that T. alkaliphila strains isolated in recent years have acquired a greater number of resistance genes and insertion sequences compared with earlier isolates.</p><p><strong>Conclusions: </strong>This study first reported the characterization of a T. alkaliphila strain carrying a novel large plasmid co-harbouring tmexC3D2-toprJ2 and tet(X6) genes, revealing the potential reservoir and transmission risk of clinically important tigecycline resistance genes.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence of tet(X4)-bearing IncFIA-IncHI1 plasmid in Citrobacter freundii from poultry in China.","authors":"Jing Wang, Kai Wang, Zhi-Hao Zhang, Zheng Su, Peng-Yun Shao, Jia-Yu Zhang, Aitiribai Abuduhelike, Xing-Xing Zhang","doi":"10.1093/jac/dkag296","DOIUrl":"https://doi.org/10.1093/jac/dkag296","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the efficiency of platform trials relative to stand-alone trials: a simulation study for the evaluation of new antibacterials.","authors":"Melissa J Hardy, Patrick N A Harris, Xiaofang Wang, Yin Mo, David L Paterson","doi":"10.1093/jac/dkag263","DOIUrl":"10.1093/jac/dkag263","url":null,"abstract":"<p><strong>Background: </strong>Serious Gram-negative bacterial infections impose significant burden, with carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Enterobacterales designated as WHO critical priority pathogens. Antibacterial registration trials are traditionally stand-alone two-arm randomized controlled trials evaluating one agent in a site-specific infection. Platform trials have been proposed as an alternative to identify new treatments more efficiently.</p><p><strong>Objectives: </strong>To evaluate the efficiency of different trial designs for treatments in serious resistant Gram-negative infections.</p><p><strong>Methods: </strong>We conducted simulation studies comparing platform trials with parallel and staggered starts and multiple stand-alone trials for serious infections caused by critical priority Gram-negative pathogens. Simulated recruitment and randomization were used to assess the impact of trial design, control type and allocation ratio on trial duration, sample size and operating characteristics.</p><p><strong>Results: </strong>In this setting, parallel or staggered platform trials reduced the sample size by 31-279 participants and the trial duration by 7-13 months compared with stand-alone trials. The staggered platform trial with concurrent controls required 11.0%-23.4% fewer participants and up to 46.8% less control participants than stand-alone trials. Across designs and scenarios, type I error and power, were consistently close to the nominal levels for all treatment-control comparisons.</p><p><strong>Conclusions: </strong>Platform trials can improve efficiency over stand-alone trials, reducing duration and sample size while maintaining operating characteristics. The improvement varies with control type, allocation ratio and staggered entry of agents and could help accelerate antibacterial development. This has implications for funders, sponsors and patients requiring access to new therapies, while recognizing ongoing operational and regulatory challenges.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}